1. Field of the Invention
The present invention relates to detection devices for determining the presence or concentration of analytes or biological agents in a sample, and more particularly, to systems using testing instruments to measure analyte activity on test strips impregnated with appropriate reagents.
2. Description of Related Art
The need for simple methods to determine the chemical and biological constituents in bodily fluids has increased as point of care testing has gained in popularity. A common application is the self monitoring of blood glucose concentrations by patients with diabetes. These patients frequently administer insulin or take other therapeutic actions based on the test results. As testing is generally recommended multiple times daily and may occur in any setting, an easy to use and relatively inexpensive method to accomplish this task is required. The costs of testing are significant to many diabetic patients, especially elderly patients with fixed incomes and those who are not reimbursed by health insurance plans.
In addition to chronic disease monitoring, there are other applications where simple, low cost testing at the point of care may be desired. For example, many practitioners believe that certain medications could be administered much more effectively, both from a medical outcomes and from a cost perspective, if the circulating level of such medications could be monitored during the course of treatment. Generally, if the level of an analyte or biological agent is important enough, the patient needs to go to a clinic or laboratory and submit to a venipuncture so a test may be run on an expensive clinical instrument. The ability to inexpensively monitor the patient either in the doctor""s office or at home could lead to improved outcomes. Given the current pressures on improving the cost effectiveness of health care, inexpensive, easy to use alternatives to expensive test methods would be welcomed.
The National Institutes of Health conducted a large scale study to evaluate the benefit of long term tight control of the blood glucose for the diabetic patient. The study, known as the DCCT, proved that long term tight control of the blood glucose levels in patients had a direct relationship to the health of the patient. One way for the medical profession to monitor the control of a patient is for the patient to use a blood glucose monitoring system which has a memory unit to record the blood glucose level and other data such as date and time.
Many diabetics currently use a test method described in U.S. Pat. No. 5,304,468 to Phillips et al. This system is comprised of an electronic meter and a disposable reagent strip. The meter reads the color change of the strip which correlates to the concentration of the analyte in the sample applied to the strip. The meter is an expensive and complex instrument which uses multiple light sources or detectors to isolate the reagent color change from the sample color. The user must select the calibration code for the meter to match the calibration code of the test strips. In this way, the meter accommodates a wide range of test strip performance values.
U.S. Pat. No. 4,637,403 to Garcia et al. describes an integrated system which provides a method by which the patient lances the finger to get a sample of blood which is then used by the device to read the quantity of analyte in the sample. This system uses a complex reflectance system to read the analyte level in the sample.
U.S. Pat. No. 5,279,294 to Anderson et al. describes a hand held shirt pocket device for quantitative measurement of glucose or analytes in biological fluids. The device has a sophisticated electronics system and a sampling system integrated into one device to determine the quantity of analyte in a bodily fluid sample
U.S. No. Pat. 5,515,170 to Matzinger et al. describes the difficulties of keeping a strip holder and optics system clean and the need to present the test strip in the proper perspective to the optics.
European Patent Specification 0 351 891 B1 Hill et al. describes an electrochemical system and electrodes which are suitable for the in vitro determination of blood glucose levels. The system requires the use of expensive electrodes and a sophisticated reader to determine blood glucose levels.
U.S. Pat. No. 4,994,167 to Shults et al. describes a measuring device for determining the presence and amount of a substance in a biological fluid using electrochemical methods. This system requires a complex instrument and method for the patient to determine the quantitative result.
U.S. Pat. No. 5,580,794 to Allen et al. describes a single use disposable measuring device for determining the presence and amount of a substance in a biological fluid using reflectance methods. This system utilizes an optics and electronics package which are mated in a single plane.
Single use disposable devices have been designed for the analysis of analytes in bodily fluids. U.S. Pat. No 3,298,789 to Mast describes a system in which whole blood is applied to a reagent strip. After a precise, user-timed interval, the blood must be wiped off by the user. An enzyme system reacts with the glucose present in the sample to create a color change which is proportional to the amount of glucose in the sample. The strip may be read visually, by comparing to a printed color intensity scale, or in an electronic instrument.
U.S. Pat. No. 5,418,142 to Kiser et al. describes a single use device which does not require blood removal or color matching. The amount of analyte present in the sample is read in a semiquantitative fashion.
U.S. Pat. No. 5,451,350 to Macho et al. describes a single use system for the determination of an analyte in a biological sample.
U.S. Pat. 5,522,255 to Neel et al. describes a fluid dose, flow and coagulation sensor for a medical instrument which uses a non-volatile electronic calibration device in the system to check the calibration of the reagent strip.
U.S. Pat. No. 5,053,199 to Keiser et. al. describes an electronically readable information carrier for use with a medical device.
U.S. Pat. No. 5,366,609 to White et. al. describes a biosensing meter with a pluggable memory key. This device uses a pluggable memory key which is used to control the operations of the meter.
U.S. Pat. No. 5,307,263 to Brown describes a modular microprocessor based health monitoring system designed to collect data from a health monitoring test system such as a blood glucose monitoring meter.
Although many improvements have been made, the cost and complexity of measuring analyte levels in biological samples remains a significant issue for patients and for the health care system. Even patients who are covered for blood glucose monitoring supplies must often purchase the meter and await reimbursement. The need to match the calibration of a meter and the strips or electrodes in use leads to errors in performance and adds cost and complexity for the manufacturers. The availability of a low cost, simplified quantitative test system for the periodic monitoring of constituents of biological fluids, such as glucose in blood, would make testing more accessible to patients and would improve their well-being and reduce the cost of their care.
Currently, existing calibration mechanisms require the loading of a calibration chip, calibration strip, inputting of a calibration code or use of a machine readable mechanism on the strip to modify the reaction interpretation of the meters. These methods can result in errors in reading of the analyte being tested for by using either the wrong calibration device with a lot of strips or entering the wrong calibration code for the lot of strips.
In addition, a system which requires a smaller fluid sample would be attractive to many patients. There has been a trend toward smaller sample sizes, but most devices still require about 10 xcexcL of blood. Many patients have difficulty routinely applying an adequate sample to the strips or electrodes. Inadequate sampling can cause erroneous results or may require that the user discard an expensive test strip and repeat the sample application procedure.
An additional issue is the use of out of date test strips with the meter. Currently the expiration date and expiration period after opening is printed on the container for the test strips. This presents a problem for the patient if he or she does not observe the dating information on the container. The strips can result in an error in the reading which can cause false response/treatment by the patient.
The invention overcomes the deficiencies of the prior art by providing a low cost testing instrument and single use test strips capable of reading small sample sizes, e.g. 3 xcexcL, and determining the amount of an analyte in the small sample. The low cost nature of the testing instrument permits the packaging of the testing instrument and test strips together in a package, creating a synchronized system which may be used to perform a specific number of tests. The testing instrument is provided at no extra cost to the user, who benefits from having a fresh device with each new package of test strips purchased. This eliminates the need for the patient to make an investment in test equipment to monitor a specific condition or therapy.
In an alternate configuration, the device may be provided as part of a starter package including a sampling device and test strips. Replacement test strips could be purchased separately without the device or sampler if longer testing instrument life is preferable. For example, the desire to include additional features such as data management capabilities could add cost which would favor a longer useful life for the testing instrument.
The testing instrument incorporates a molded lens optic system consisting of one or more channels and a simple electronics package consisting of light emitting diodes (LEDs), analog to digital conversion electronics, a processor unit, Read Only Memory and a digital display system. The testing instrument case has a positioning system which interfaces with the test strip to create positive location and alignment for the reagent test pad within the strip and the optics.
The applied bodily fluid reacts with the reagents impregnated in the test pad within the test strip and the resulting color change is read by the optics system. The signal is converted and displayed on the digital readout as the concentration of the analyte in the sample.
An advantageous feature in accordance with the invention is the use of a small sample sizes, e.g., about 3 xcexcL, which is a fraction of the volume required for most blood glucose tests and could be more readily obtained by patients.
Another advantageous feature in accordance with the invention is the provision of a simple low cost testing instrument and a complimentary reagent test strip.
Another advantageous feature in accordance to the invention is the use of reagent test strips that are calibrated to the testing instrument and/or an intelligent calibration device which may each be one-time readable mechanisms, eliminating the potential problems of re-use of the calibration device with the wrong set of test strips.
Another advantageous feature in accordance with the invention is a testing instrument which is precalibrated or synchronized to the lot of reagents test strips with which it is supplied, eliminating the need for the user to match or enter calibration information.
Another advantageous feature in accordance with the invention is a system which is designed for a predetermined number of test results, minimizing upkeep such as cleaning or battery replacement.
Another advantageous feature in accordance with the invention is the elimination of the need for a separate test strip holder, simplifying the interface of the disposable portion of the test system with the re-usable testing instrument.
Another advantageous feature in accordance with the invention is the elimination of the need for a patient to calibrate the meter for the test strips or keep track of expiration dating by placing the information on a single use calibration chip.